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. 2024 Jan;16(2):109-125.
doi: 10.2217/epi-2023-0248. Epub 2024 Jan 16.

Using saliva epigenetic data to develop and validate a multivariable predictor of esophageal cancer status

Timothy C Stone  1 , Vanessa Ward  1 , Aine Hogan  1 , Kai Man Alexander Ho  1   2 , Ash Wilson  1 , Hazel McBain  2 , Margaret Duku  2 , Paul Wolfson  1 , Sharon Cheung  1 , Avi Rosenfeld  3 , Laurence B Lovat  1   2   4 ; SPIT Study Group Collaborators:
Collaborators, Affiliations

Using saliva epigenetic data to develop and validate a multivariable predictor of esophageal cancer status

Timothy C Stone et al. Epigenomics. 2024 Jan.

Abstract

Background: Salivary epigenetic biomarkers may detect esophageal cancer. Methods: A total of 256 saliva samples from esophageal adenocarcinoma patients and matched volunteers were analyzed with Illumina EPIC methylation arrays. Three datasets were created, using 64% for discovery, 16% for testing and 20% for validation. Modules of gene-based methylation probes were created using weighted gene coexpression network analysis. Module significance to disease and gene importance to module were determined and a random forest classifier generated using best-scoring gene-related epigenetic probes. A cost-sensitive wrapper algorithm maximized cancer diagnosis. Results: Using age, sex and seven probes, esophageal adenocarcinoma was detected with area under the curve of 0.72 in discovery, 0.73 in testing and 0.75 in validation datasets. Cancer sensitivity was 88% with specificity of 31%. Conclusion: We have demonstrated a potentially clinically viable classifier of esophageal cancer based on saliva methylation.

Keywords: biomarker panel; diagnosis; epigenetics; esophageal adenocarcinoma; saliva.

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Conflict of interest statement

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.. CONSORT diagram.
Figure 2.
Figure 2.. Plot of Kolmogorov–Smirnoff distance metric for biological duplicates showing distances between duplicates (x-axis) and distances from each array to a summarized average array (y-axis).
Figure 3.
Figure 3.. Heat map plot of p-values of first ten principal component analysis components (A) before and (B) after plate-fitted residual correction for experiment batch, array row, age, sex, disease diagnosis and epithelial cell content.
The components were statistically tested against experiment, array plate row, age, sex, disease status and epithelial cell content. The plate-fitted residuals show p = 1.00. Blue = low p-value; red = high p-value.
Figure 4.
Figure 4.. Module membership after repeated classification with modification of five samples (3%) of the discovery cohort.
Figure 5.
Figure 5.. Receiver operating characteristic curve of the most successful classifiers for the discovery set, testing set and validation dataset.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J. Clin. 71(1), 7–33 (2021). - PubMed
    1. Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet 381(9864), 400–412 (2013). - PubMed
    1. Huang J, Koulaouzidis A, Marlicz W et al. Global burden, risk factors, and trends of esophageal cancer: an analysis of cancer registries from 48 countries. Cancers 13(1), 141 (2021). - PMC - PubMed

    2. •• Excellent overview of the global burden and distribution of esophageal cancer.

    1. Fitzgerald RC, di Pietro M, Ragunath K et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut. 63(1), 7–42 (2014). - PubMed
    1. Haidry R, Lovat L. Long-term durability of radiofrequency ablation for Barrett’s-related neoplasia. Curr. Opin. Gastroenterol. 31(4), 316–320 (2015). - PubMed

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